Does a higher arachidonic acid-to-EPA ratio suggest a more pro-inflammatory balance and impaired endothelial function?

In an 83-year-old man, an elevated arachidonic acid (AA)-to-EPA ratio can provide biologically relevant context about fatty-acid balance and vascular risk, but it is not a diagnostic inflammatory test or an established treatment target.

Inflammation and cardiovascular relevance

• A higher AA:EPA ratio is plausibly a relatively pro-inflammatory substrate profile. AA and EPA compete for cyclooxygenase/lipoxygenase metabolism: AA supplies 2-series prostanoids and 4-series leukotrienes, whereas EPA supplies generally less-potent 3-series/5-series analogues and precursors of E-series resolvins.
• This does not establish systemic inflammation in an individual. Raising dietary AA increases tissue AA but generally has not changed CRP, TNF-α, IL-6, PGE₂, or lipoxin A₄ in intervention studies, despite modest increases in stimulated-cell eicosanoid production.
• In the observational Hisayama cohort, each 0.20 decrease in EPA:AA (therefore a higher AA:EPA ratio) was associated with 52% higher cardiovascular risk among participants with hs-CRP ≥1.0 mg/L, suggesting that inflammatory status may modify the association.

Endothelial function

• The vascular evidence is directionally consistent: in hypertriglyceridemia, purified EPA increased brachial flow-mediated dilation (FMD) from 4.16% to 6.30%; improvement correlated with the rise in EPA:AA (r=0.34, p=0.014). Coronary-disease studies likewise observed concurrent increases in EPA:AA and FMD.
• A 2023 GRADE systematic review/meta-analysis of 32 studies found n-3 PUFA supplementation improved brachial FMD by 0.8 percentage points, though heterogeneity was substantial.

Interpretation

• EPA may support nitric-oxide bioavailability and endothelial nitric-oxide-synthase coupling while reducing oxidative and inflammatory signaling. However, triglyceride changes may explain some FMD improvement, rather than the ratio itself.

Bottom line

• A high AA:EPA ratio is a plausible marker of a less favorable inflammatory/vascular milieu and potentially poorer endothelial function, but it is not a validated standalone inflammatory biomarker, causal measure, or ratio-specific treatment target.